UPDATES IN MOLECULAR TESTING

AND FRONT-LINE TREATMENT IN

OVARIAN CANCER
Bradley J. Monk, MD, FACS, FACOG

Florida Cancer Specialists and Research Institute

Medical Director Late-Phase Clinical Research
West Palm Beach, FL 33401
[email protected]

Vice President and Member Board of Directors GOG-Foundation

Director GOG-Partners
[email protected]
 Disclosures Relative to This Presentation

Honorarium and consulting from:

– AstraZeneca
– Pharma& (Clovis)
– Genentech/Roche
– GSK (Tesaro)
– Merck
– Myriad
 Sir Richard Branson
(Virgin Atlantic/Virgin Galactic Innovator)
 Potential Cellular Origins of
Ovarian Carcinomas
Ovarian
Surface High-Grade
Epithelium Serous
Carcinoma
Fallopian
Tube
Ovarian Surface
Uterus
Epithelium
Low-Grade
Serous
Carcinoma
Ovary Cervix Fallopian
Tube Fallopian Tube
Vagina
Epithelium Epithelium Clear Cell
Carcinoma

Retrograde
Endometrium
Menstruation?
Endometrioid
Endometrium Carcinoma
Endometriosis

Mucinous
Carcinoma

Unknown
Committee on the State of the Science in Ovarian Cancer Research. Board on Health Care Services. Institute of Medicine. National
Academies of Sciences, Engineering, and Medicine . Ovarian Cancers: Evolving Paradigms in Research and Care. National Academies Press
(US); Washington, DC, USA: 2016.
 Epithelial Ovarian Cancer Subtypes Are Associated
With Different Mutations and Molecular Aberrations
Epithelial ovarian cancer can be characterized as a heterogeneous disease, not only
histologically, but through identification of distinct molecular pathway alterations

Epithelial

High-grade Low-grade
Mucinous1 Clear cell1 Endometrioid1,2
serous1 serous1
TP53 BRAF KRAS ARID1A ARID1A
BRCA1 and BRCA2 KRAS HER2 amplification PIK3CA PIK3CA
NF1 NRAS PTEN PTEN
RB1 ERBB2 CTNNB1 CTNNB1
CDK12 PPP2R1  PPP2R1 
HR repair genesa MMR deficiency
a CHK2, BARD1, BRIP1, PALB2, RAD50, RAD51C, ATM, ATR, EMSY, and Fanconi anemia genes.

HR, homologous recombination; MMR, mismatch repair.

1. Banerjee S, et al. Clin Cancer Res. 2013;19(5):961-8. 2. McConechy MK, et al. Mod Pathol. 2014;27(1):128-34.
 First-Line Chemotherapy [Historical] Standard of Care:
Every 3 week IV Carboplatin and Paclitaxel
ICON8 Progression-Free Survival Weekly Weekly
1.00 Standard
paclitaxel carbo-paclitaxel
(n=522)
(n=523) (n=521)
Progression-Free Survival

Standard
0.75 Weekly paclitaxel Progressions 330 (63%) 335 (64%) 338 (65%)
Weekly carbo-paclitaxel
(proportion)

Median PFS,
17.9 20.6 21.1
mo
0.50
Log rank
P=0.45 P=0.56
(vs standard)

0.25 HR vs Standard 0.92 0.94

(97.5% CI) (0.77–1.09) (0.79–1.12)

0.00 Restricted
24.4 months 24.9 months 25.3 months
0 6 12 18 24 30 36 42 48 54 60 66 means
No. at risk
Time from Randomisation (months)
Standard 522 471 354 250 198 130 92 59 32 18 3 1
Weekly paclitaxel 523 489 383 279 210 144 92 59 28 17 3 0
Weekly carbo-paclitaxel 521 468 385 281 208 153 99 66 33 15 6 0

Weekly dose-dense chemotherapy can be delivered successfully as first-line epithelial ovarian cancer treatment without
substantial toxicity increase; it does not significantly improve PFS compared to standard 3 -weekly chemotherapy

CI=confidence interval; HR=hazard ratio; PFS=progression-free survival.

Clamp AR et al. Presented at: ESMO Annual Meeting; 2017.
Lancet Oncol 2022 Jul;23(7):919-930.
Phase III GOG-218 Study of Adjuvant Chemotherapy
+ Bevacizumab: Design
GOG-2182 (NCT00262847) was a double-blinded, randomized, controlled phase 3
trial that included 1,873 women with stage III-IV disease, all of whom received CT.
b Participants randomized to: CT + placebo (PBO, cycles 2–22; control), CT + bev

(bev, 15 mg/kg cycles 2–6), followed by PBO (cycles 7–22, bev-initiation), or CT +

bev (15 mg/kg cycles 2–22, bev-throughout)

Primary endpoint: PFS

Baseline characteristics:
• 40% suboptimally
resected stage III
• 26% stage IV

Burger RA et al N Engl J Med. 2011 Dec 29;365(26):2473-83. FDA Approved June 2018
Tewari KS et al J Clin Oncol. 2019 Sep 10;37(26):2317-2328.
 Phase 3 GOG-218 Study of Adjuvant Chemotherapy +
Bevacizumab: Efficacy Outcomes
Final OS (103 month follow up)
PFS (Primary Endpoint)
Bev Bev Control
Throughout Initiation (CPP)
(CPB15+) (CPB15)
mPFS (mo) 18.2 12.8 12.0

Median OS: 39.3 mo, control;

HR (95% CI) 0.62 (0.52, 0.75) 0.83 (0.70, 0.98)
38.7 mo, bev-initiation, and
P-value < 0.0001 NS
39.7 mo, bev-throughout

18.2 mo

12.0 mo

No survival differences
observed with addition of
bevacizumab compared with
Burger RA et al N Engl J Med. 2011 Dec 29;365(26):2473-83. CT alone
Bevacizumab. Prescribing Information. Genentech. 2020. Burger RA, et al. N Engl J Med.
2011;365:2473-2483. Tew ari K, et al. J Clin Oncol. 2019;37:2317-2328
Tewari KS et al J Clin Oncol. 2019 Sep 10;37(26):2317-2328.
 PARP Inhibitor Exploits the Baseline Vulnerability
of Cells With Inherent DNA Repair Deficiency 1
PARP
inhibitor

PARP
PARP
inhibitor
Increase in DSBs
PARP
in replicating cells

Trapped PARP on
SSBs
DSBs

HRR-deficient cancer cell Normal cell

 ✓
Reliance on error-prone Repair of DSBs via
pathways leads to DNA the HRR pathway and
damage accumulation cell survival
and cell death
1. O’Connor MJ. Mol Cell. 2015;60:547-560.
 How to Identify Homologous Recombination Deficiency1,a

myChoice FoundationOne LOH

(CDx olaparib, niraparib) (CDx rucaparib, olaparib)

myChoice HRD
Score

Loss of Telomeric Large-scale LOH

heterozygosity allelic state
(LOH) imbalance transitions
(TAI) (LST)
HR status is determined by genomic instability score • HRR pathway–related genes
(GIS) BRCA (germline, somatic)
• HR-deficient tumors: tissue GIS ≥42 OR a BRCAm • Non-BRCA HRR gene mutations
• HR-proficient tumors: tissue GIS <42 (eg, RAD51C, RAD51D, BRIP1, ATM,
• HR not determined CDK12, CHEK1, CHEK2)

aTests have not been compared head to head. Paired w ith development of respective drugs.
1. https://w ww.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm.
 Pharmacologic Properties of PARP Inhibitors
May Impact Tissue Concentration
How much? For how long? How metabolized? To where?
Tissue
Bioavailability Half-life Metabolism distribution
PARP inhibitor
F (%) t1/2 (h) (Major enzymes) Vd/F (L)

Niraparib1 73 36 CEs 1220

Olaparib2 NA 11.9 ± 4 CYP3A4 167

Rucaparib3 36 17–19 CYP2D6 113–262

PARP inhibitors differ in terms of biochemical properties. Hence, data cannot be

extrapolated from one PARPi to another
Each PARPi needs to be assessed based on its approved indication and data

CE = carboxy lesterase; NA = not av ailable; PARP = poly (ADP-ribose) poly merase.

1. ZEJULA® (niraparib) capsules [prescribing inf ormation]. Waltham, MA: TESARO, Inc.; 2017. 2. LY NPARZA® (olaparib) tablets
[prescribing inf ormation]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017. 3. RUBRACA ® (rucaparib) tablets [prescribing
inf ormation]. Boulder, CO: Clov is Oncology , Inc.; 2018. 4. Farmer H, et al. Nature. 2005;434(7035):917-921.
 Common Adverse Events With
PARP Inhibitors in Ovarian Cancer

Hematologic Nonhematologic Rare

GI: Nausea/vomiting/
Neutropenia AML
diarhea/constipation

Anemia Asthenia/fatigue MDS

Thrombocytopenia LFTs and HTN Pneumonitis

 Milestones in the Evolution of Maintenance Therapy in
Advanced Ovarian, Peritoneal and Tubal Cancer
Year of publication:
NOVA6 PRIMA11 NORA13 OVARIO14* PRIME16*
Niraparib Niraparib Niraparib Niraparib + Niraparib
≥2Lm 1Lm 1Lm bevacizumab 1Lm
1Lm

2003 2011 2012 2016 2017 2018 2019 2020 2021 2022

GOG-0218/ SOLO28 PAOLA-112 OReO15*

Olaparib SOLO110
ICON72,3 Olaparib Olaparib + Olaparib
Bevacizumab OCEANS5 ≥2Lm BRCAm ≥2Lm
1Lm Bevacizumab 1Lm BRCAm bevacizumab
ARIEL39 1Lm
2Lm Rucaparib ATHENA-MONO17
≥2Lm Rucaparib
1Lm
GOG-01781 Study194 GOG-02137
Paclitaxel Olaparib Bevacizumab
1Lm ≥2Lm 2Lm

*Data presented at congresses prior to primary publication.

1Lm, first-line maintenanc e; 2Lm, second-line maintenance; BRCAm, breast cancer gene mutant; OC, ovarian cancer; PARPi, poly(ADP-ribose)polymer as e inhibitor.
1. Markman M, et al. J Clin Oncol 2003;21:2460 –5; 2. Burger RA, et al. N Engl J Med 2011;365:2473–83; 3. Perren TJ, et al. N Engl J Med 2011;365:2484–96; 4. Ledermann J, et al. N Engl J Med 2012;366:1382 –92; 5. Aghajanian C, et
al. J Clin Oncol 2012;30:2039–45; 6. Mirza MR, et al. N Engl J Med 2016;375:2154–64; 7. Coleman R, et al. Lancet Oncol 2017;18:7 79–91; 8. Pujade-Laurai ne E, et al. Lancet Oncol 2017;18:1274–84; 9. Coleman R, et al. Lancet
2017;390:1949–61; 10. Moore K, et al. N Engl J Med 2018;379:2495 –505; 11. González Martín A, et al. N Engl J Med 2019;381:2391 –402; 12. Ray-Coquard I, et al. N Engl J Med 2019;381:2416–28; 13. Wu XH, et al. Ann Oncol
2021;32:512–21; 14. Hardesty MM, et al. presented at SGO 2021, 19–25 Mar (virtual); 15. Pujade-Laur aine E, et al. presented at ESMO 2021; 16–21 Sep (virtual); 16. Li N, et al. presented at SGO 2022, 18–21 Mar, Phoenix, AZ; 17.
Monk BJ, et al. J Clin Oncol 2022: https://doi.org/10.1200/JCO.22.01003
13
 First-Line Maintenance in Patients
With Newly Diagnosed Advanced Ovarian Cancer

SOLO-1/ PRIMA/
GOG-30041 GOG-30122 Niraparib vs placebo
Olaparib vs placebo

PAOLA-13 Olaparib + bevacizumab vs ATHENA4

placebo + bevacizumab Rucaparib vs Placebo

1. Moore K et al. N Engl J Med. 2018;379:2495-2505. 2. González-Martín A et al. N Engl J Med. 2019;381:2391-2402.
3. Ray-Coquard I et al. N Engl J Med. 2019;381:2416-2428. 4. Monk BJ et al J Clin Oncol. 2022 Jun 6;JCO2201003. doi: 10.1200/JCO.22.01003. Online ahead of print
 FDA Approval: Olaparib for Maintenance Treatment1

Olaparib was approved in December 2018 for the

maintenance treatment of patients with deleterious
or suspected deleterious germline or somatic
BRCA-mutated (gBRCAm a or sBRCAm) advanced

✓
EOC, FTC, or PPC who are in a CR or PR to 1L
platinum-based chemotherapy

a Patients w ith gBRCAm advanced EOC, FTC, or PPC should be selected for therapy based on an FDA -approved companion diagnostic.
1. https://w ww.fda.gov/drugs/fda-approved-olaparib-lynparza-astrazeneca-pharmaceuticals-lp-maintenance-treatment-adult-patients.
 SOLO-1/GOG-3004: Study Design1

Olaparib 300 mg
• Newly diagnosed, FIGO stage III-IV, twice daily • Study treatment continued
high-grade serous or endometrioid (n = 260) until disease progression
ovarian, PPC, or FTC
• Patients with no evidence
• g/sBRCAm 2:1
of disease at 2 years
R Stratified by response to
• ECOG PS 0-1 platinum-based stopped treatment
chemotherapy
• Cytoreductive surgerya • Patients with a PR at
• In clinical CR or PR after platinum-based 2 years could continue
Placebo treatment
chemotherapy (n = 131)

2 years of treatment if no evidence of disease

• Primary endpoint: investigator-assessed PFS (modified RECIST v1.1)

• Secondary endpoints: PFS using BICR, PFS2, OS, time from randomization to first subsequent therapy or death,
time from randomization to second subsequent therapy or death, HRQOL (FACT-O TOI score)
aUpfront or interval attempt at optimal cytoreductive surgery for stage III disease and either biopsy and/or upfront or interv al cytoreductive surgery for stage IV disease.
1. Moore K et al. N Engl J Med. 2018;379:2495-2505.
 SOLO1/GOG 3004: OS at 7-year Follow-up
Olaparib Placebo
(N=260) (N=131)
100
Events, n (%) 84 (32.3) 65 (49.6)
90
73.1% Median OS, months NR 75.2
80
67.0% HR 0.55 (95% CI 0.40–0.76);
70
Overall survival (%)

P=0.0004*
60 63.4%
Olaparib
50
46.5%
40
30 44.3% of patients in the placebo
Placebo
group received subsequent
20 PARP inhibitor therapy,
10 compared with 14.6% of
0 patients in the olaparib group
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102
Months since randomization
No. at risk
Olaparib 260 252 246 236 227 214 203 194 185 177 170 165 159 157 153 79 21 0
Placebo 131 128 125 114 108 100 97 92 87 80 73 67 60 54 52 21 6 0
*P<0.0001 required to declare statistical significance
DiSilvestro P et al
 FDA Approval: Niraparib for Maintenance Treatment1

Niraparib was approved in April 2020 for the

maintenance treatment of patients with advanced
EOC, FTC, or PPC who are in a CR or PR to

✓
1L platinum-based chemotherapy

1. https://w ww.fda.gov/drugs/drug-approvals-and-databases/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer.
 PRIMA/GOG-3012: Niraparib in
First-Line Advanced Ovarian Cancer1,2
Treatment for 36 months or until PD
Inclusion Criteria
• High-grade serous or endometroid Niraparib 200/300 mga
pathology Stratification
once daily
• Stage III: PDS with visible residual • NACT administered: (n = 487)
disease post surgery, NACT, or AEs or no
inoperable • Best response to 2:1
• Stage IV: PDS regardless of first platinum
R
residual disease, NACT, therapy: CR or PR
or inoperable • Tissue HR test
• CR or PR following platinum 1L status: HRD or
treatment HRP/not Placebo
• Tissue for HR testing was required determined (n = 246)
at screening (myChoice)

• Primary endpoint: PFS using BICR

• Key secondary endpoint: OS
• Secondary endpoints: PFS2, TFST, PRO, and safety

aBody w eight ≥77 kg and platelets ≥150,000/mcL started w ith 300 mg daily; body w eight <77 kg and/or platelets <150,000/mcL started w ith 200 mg QD.
1. González-Martín A et al. ESMO 2019. Abstract LBA1. 2. González-Martín A et al. N Engl J Med. 2019;381:2391-2402.
PRIMA/GOG-3012: Investigator-Assessed PFS Across Biomarker Subgroups
17 November 2021 Clinical Cutoff Date

• Niraparib treatment increased PFS duration compared with placebo treatment across biomarker subgroups
(Figure 4)
• The greatest treatment benefit was seen in patients with HRd tumours that were BRCA mutated
(hazard ratio, 0.45; 95% CI, 0.32–0.64)

Poster #530P
González-Martín A et al
 FDA Approval: Olaparib Plus Bevacizumab
for First-Line Maintenance Treatment1,a

In May 2020, the FDA approved olaparib in

combination with bevacizumab for 1L maintenance
treatment of patients with advanced EOC, FTC,
or PPC in CR or PR to 1L platinum-based
chemotherapy and whose cancer is associated

✓
with HRD-positive status defined by either a
deleterious or suspected deleterious BRCAm,
and/or genomic instability

aThe FDA also approved the Myriad myChoice CDx as a companion diagnostic for olaparib.
1. https://w ww.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-plus-bevacizumab-maintenance-treatment-ovarian-fallopian-tube-or-primary.
 PAOLA-1: Study Design1,2

Maintenance
Inclusion Criteria
Olaparib
• Newly diagnosed, FIGO
First Line 300 mg twice daily
stage III-IV, high-grade NED/CR/PR + bevacizumabd
serous/endometrioid ovarian • Surgery (upfront or
2:1 x 2 years
cancer, FTC, or PPCa interval)
• Platinum-taxane–based R
Stratification chemotherapy
• Tumor BRCAm statusb Placebo
• ≥3 cycles of
• 1L treatment outcomec + bevacizumabd
bevacizumabd
x 2 years
(N = 806)

• Primary endpoint: investigator-assessed PFS (RECIST v1.1)

• Sensitivity analysis: PFS by BICR
• Secondary endpoints: TFST, PFS2, TSST, OS, HRQOL, safety, and tolerability
aPatients w ith other epithelial nonmucinous ovarian cancer w ere eligible if they had a germline BRCA1 and/or BRCA2 mutation. b By central labs.
cAccording to timing of surgery and NED/CR/PR. d Bevacizumab: 15 mg/kg Q3W for a total of 15 months, including w hen administered w ith chemotherapy.
1. Ray-Coquard I et al. N Engl J Med. 2019;381:2416-2428. 2. Ray-Coquard I et al. ESMO 2019. Abstract 3955.
 PAOLA-1: OS in the HRD-positive Subgroup
Olaparib + Placebo +
100 bevacizumab bevacizumab
90 (N=255) (N=132)

5-year OS rate Events, n (%)

Patients who survived (%)

80 93 (36.5) 69 (52.3)

70 65.5% Median OS, months 75.2 (unstable)* 57.3

60 5-year OS rate, % 65.5 48.4
50
48.4% HR 0.62 (95% CI 0.45–0.85)
40
38% reduction in risk of death for olaparib +
30
bevacizumab vs bevacizumab alone
20
Patients receiving a PARP inhibitor
10 during any subsequent treatment
Olaparib + bevacizumab: 17.3% (44/255)
0
0 12 24 36 48 60 72 80 Placebo + bevacizumab: 50.8% (67/132)

No. at risk
Time from randomization (months)
Olaparib + bev acizumab 255 253 253 252 252 244 238 231 225 215 205 200 195 189 183 176 174 170 164 142 116 83 62 32 17 4 0
Placebo + bev acizumab 132 130 129 128 126 121 117 114 109 105 100 96 91 89 86 82 79 77 70 59 44 29 21 9 2 1 0

*Median unstable; <50% data maturity.

HRD positive defined as a tBRCAm and/or genomic instability score of ≥42 on the Myriad myChoice HRD Plus assay.
Isabelle Ray-Coquard
ATHENA–MONO (GOG-3020/ENGOT-ov45):
A Randomized, Double-blind, Phase 3 Trial Evaluating
Rucaparib Monotherapy Vs Placebo As Maintenance
Treatment Following Response To First-line
Platinum-based Chemotherapy In Ovarian Cancer
Bradley J. Monk,1 Christine Parkinson,2 Myong Cheol Lim,3 David M. O’Malley,4 Ana Oaknin,5 Michelle K. Wilson,6
Robert L. Coleman,7 Domenica Lorusso,8 Amit Oza,9 Sharad Ghamande,10 Athina Christopoulou,11 Emily Prendergast,12
Fuat Demirkiran,13 Ramey D. Littell,14 Anita Chudecka-Głaz,15 Mark A. Morgan,16 Sandra Goble,17 Stephanie Hume,17
Keiichi Fujiwara,18 Rebecca S. Kristeleit19

1GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ, USA; 2Addenbrooke’s Hospital,
Cambridge, UK; 3National Cancer Center Korea, Goyang-si, Gyeonggi-do, Republic of Korea; 4The Ohio State University, James Cancer Center, Columbus, OH, USA; 5Vall d’Hebron Institute
of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 6Auckland City Hospital, Auckland, New Zealand; 7US Oncology
Research, The Woodlands, TX, USA; 8MITO and Fondazione Universitario A. Policlinico Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy; 9Princess Margaret Hospital
Cancer Centre, Toronto, Ontario, Canada; 10Augusta University, Augusta, GA, USA; 11St. Andrews General Hospital, Patras, Greece; 12Minnesota Oncology and Metro-Minnesota Community
Oncology Research Consortium, Minneapolis, MN, USA; 13Istanbul University, Cerrahpaşa, Istanbul, Turkey; 14Kaiser Permanente Northern California Gynecologic Cancer Program, San
Francisco, CA, USA; 15Pomeranian Medical University, Szczecin, Poland; 16University of Pennsylvania Health System, Philadelphia, PA, USA; 17Clovis Oncology, Inc., Boulder, CO, USA;
18Saitama Medical University International Medical Center, Hidaka, Saitama, Japan; 19Guy’s and St Thomas’ NHS Foundation Trust, London, UK

Bradley J. Monk, MD, FACS, FACOG (LBA5500)

 ATHENA–MONO Study Schema
Key Patient Eligibility Randomization 4:4:1:1 Study Analyses
• Newly diagnosed, stage III–IV, high- Arm A (n≈400) ATHENA–MONO
grade epithelial ovarian, fallopian rucaparib 600 mg BID PO + Treatment for 24
Arm B (n≈400)
tube, or primary peritoneal cancer nivolumab 480 mg IV months*, or until
rucaparib 600 mg BID PO +
• Completed frontline platinum-doublet Arm B (n≈400)
radiographic
progression, placebo IV
chemotherapy and surgery rucaparib 600 mg BID PO +
– Achieved investigator-assessed unacceptable toxicity, Arm D (n≈100)
placebo IV or other reason for placebo PO +
CR or PR
– Received cytoreductive surgery Arm C (n≈100) discontinuation placebo IV
(primary or interval; R0/complete placebo PO +
resection permitted) nivolumab 480 mg IV
ATHENA–COMBO
• ECOG PS 0 or 1 Arm D (n≈100)
Arm A (n≈400)
• No prior treatment for ovarian cancer, placebo PO +
rucaparib 600 mg BID PO +
including any maintenance treatment, placebo IV
nivolumab 480 mg IV
other than frontline platinum regimen Randomization Stratification Factors
• Tumor HRD test status † Arm B (n≈400)
rucaparib 600 mg BID PO +
• Disease status post-chemotherapy
placebo IV
• Timing of surgery

*After initiation of oral/IV combination study treatment (IV drug was initiated cycle 2 day 1; 28 -day cycles). †Centrally assessed, determined by FoundationOne CDx (BRCAmut, BRCA wt/LOHhigh [LOH
≥16%], BRCA wt/LOHlow [LOH <16%], BRCAwt/LOHindeterminate). BID, twice daily; BRCA, BRCA1 or BRCA2; CR, complete response; ECOG PS, Eastern Cooperative Oncology Group performance status;
HRD, homologous recombination deficiency; IV, intravenous; LOH, loss of heterozygosity; mut, mutant; PO, by mouth; PR, partia l response; wt, wild type.

Bradley J. Monk, MD, FACS, FACOG (LBA5500)

PDUFA Date June 25, 2023
https://s22.q4cdn.com/778348918/files/doc_financials/2022/q3/8d6f0174-be19-4166-8f15-b9b0f26649ff.pdf
26
Primary Endpoint – Investigator-Assessed PFS: HRD
Population Median 95% CI
100 Rucaparib 28.7 23.0–NR
Progression-free survival (%)

90 Placebo 11.3 9.1–22.1

80 73.8% Log-rank P=0.0004
70 HR, 0.47; 95% CI, 0.31–0.72
60 56.3%
50 47.7%
40 35.0%
30
20
Cumulative event rate:
10 Rucaparib, 43.2%; Placebo, 63.3%
0
0 3 6 9 12 15 18 21 24 27 30 33 36 39
Months
Patients at risk (events)
Rucaparib 185(0) 175(3) 165(12) 143(31) 127(46) 110(60) 100(66) 82(71) 59(74) 36(78) 22(79) 12(80) 3 (80) 0 (80)
Placebo 49(0) 43(5) 35(13) 32(16) 22(25) 21(26) 18(28) 11(29) 8 (30) 4 (31) 2 (31) 0 (31)

Data cutoff date: March 23, 2022.

HR, hazard ratio; HRD, homologous recombination deficiency; NR, not reached; PFS, progression-free survival.

Bradley J. Monk, MD, FACS, FACOG (LBA5500)

27
Primary Endpoint – Investigator-Assessed PFS: ITT
Population Median 95% CI
100 Rucaparib 20.2 15.2–24.7
Progression-free survival (%)

90 Placebo 9.2 8.3–12.2

80 Log-rank P<0.0001
70 HR, 0.52; 95% CI, 0.40–0.68
63.0%
60
45.1%
50
40 42.1%
30 25.4%
20
Cumulative event rate:
10 Rucaparib, 53.9%; Placebo, 70.3%
0
0 3 6 9 12 15 18 21 24 27 30 33 36 39
Months
Patients at risk (events)
Rucaparib 427 (0) 398 (15) 351 (57) 298 (101) 245 (149) 213 (176) 190 (193) 151 (207) 114 (214) 67 (224) 42 (226) 23 (229) 7 (230) 0 (230)
Placebo 111 (0) 97 (11) 72 (34) 60 (44) 42 (61) 39 (64) 31 (69) 18 (75) 14 (76) 8 (78) 5 (78) 3 (78) 1 (78) 0 (78)

Data cutoff date: March 23, 2022.

HR, hazard ratio; ITT, intent-to-treat; PFS, progression-free survival.

Bradley J. Monk, MD, FACS, FACOG (LBA5500)

 Frontline Ovarian Cancer

BRCA-associated
HRD HRP
cancers

Bevacizumab with
Olaparib switch and to follow
Niraparib (Rucaparib)
maintenance chemotherapy
switch maintenance
(± bevacizumab)
Niraparib (Rucaparib)
switch maintenance

Niraparib (Rucaparib) Olaparib +

switch maintenance bevacizumab No maintenance
 Integrated Maintenance Treatment Paradigm for
Supporting Phase 3
Use in 1-L Ovarian Cancer (2020) NEJM Publications
BRCA mut
HRD: SOLO-1
Decision #1 Add PARPi PRIMA
(preferred)
NACT vs ATHENA
Primary debulking No bevacizumab
HRP:
Testing PRIMA
Add PARPi
- Germ line
panel testing (all or ATHENA
EOC) IV q 3 week Observation
carboplatin +
- Tumor HRD paclitaxel
testing (if germ BRCA mut
line BRCAwt) HRD: PAOLA-1
Bevacizumab Add PARPi
Decision #2 during (preferred)
Bevacizumab Y/N chemotherapy and
in maintenance
1. NACT = Neoadjuvant chemotherapy HRP: GOG 218
2. EOC=Epithelial ovarian cancer Chan JK, Liang SY, Kapp DS,
3. HRD = Homologous recombination deficient Chan JE, Herzog TJ, Coleman Continue GOG 262
4. HRP = Homologous recombination proficient RL, Monk BJ, Richardson MT. Decision #3 bevacizumab
5. PARPi = Poly ADP Ribose inhibitor Gynecol Oncol. 2020 29
6. NEJM = New England Journal of Medicine Dec;159(3):604-606. Add PARPi?
 Florida Cancer Specialists and Research
Institute

Founded in 1984
98 offices, 93 clinical sites
250+ physicians
285+ nurse practitioners and physician assistants
Patients in 2023*:
▪ 83,711 new patients
▪ 127,460 unique patients
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* as of 11/30/23